Blood substitutes as pharmacotherapies in clinical practice

To discuss the development and current status of blood substitutes, including hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbons. Research in this field offers an important view into the future of transfusion medicine in the operating room, as well as in trauma and combat arenas.

A pivotal multinational phase III trial of the Biopure product HBOC-201 (Hemopure) has been completed in orthopedic surgery patients. HBOC-201 consists of polymerized bovine hemoglobin and has already been well tolerated in patients undergoing cardiopulmonary bypass and abdominal aortic reconstruction. Polyheme is a polymerized human hemoglobin in early phase III clinical trials with trauma patients, having infused up to 10,000 ml, with efficacy apparently demonstrated in phase II. The Sangart product, Hemospan, is currently undergoing phase II trials.

Polymerized hemoglobin preparations have proven most successful in clinical trials due to their improved side-effect profile. The goal is to evaluate blood substitutes with enhanced intravascular retention, reduced osmotic activity, and attenuated hemodynamic derangements such as vasoconstriction. Although not without substantial morbidity and mortality, the current safety of allogeneic blood transfusion demands that comparative studies show minimal adverse effects, as well as efficacy and potential for novel applications.